Despite major advances in the diagnosis and treatment of human lymphomas, the clinical behavior for many patients with a particular subtype of lymphoma remains unpredictable. Since host immunological mechanisms play an important role in lymphoma biology, a greater understanding of tumor host relationships in vivo should help in determining which tumor cell and host cell features are most important in predicting clinical outcome. This project will address three major aspects of the tumor host interaction in vivo: (1) the type and number of effector cells in lymphoma subgroups, (2) the numbers of tumor cells and proliferating cells in lymphoma subgroups, (3) the degree of expression of the common lymphoma-associated proto-oncogene product BCL-2 and of the multidrug resistance marker "P-glycoprotein" in lymphoma subgroups. Studies of sequential biopsies from follicular lymphoma patients may provide insights in tumor progression/transformation. Ongoing studies will rely on frozen section immunohistochemical staining but increasingly will utilize antibodies reactive with fixation-resistant epitopes. Recently developed monoclonal antibodies against cytotoxic cells, memory cells, homing-associated molecules, and PCNA/Cyclin will be utilized. Gene rearrangement studies will also be performed in particular lymphoma subgroups. Quantitation of immunostained cells both in frozen and paraffin sections will employ video densitometry/image analysis. Methods will be developed for studying lymphokines and their receptors in lymphoma cells and host cells. Increased usage of dual label tissue section immunohistochemical methods will allow precise identification of lymphoma cells vs host cell expression of the various biological markers. Correlations with clinical behavior remain the major focus of this work. The identification of clinically important immunological parameters may aid physicians in the selection of a particular treatment modality, provide the rationale for delay of treatment and may prove useful in devising experimental treatment strategies. Long-term goals are to devise a more reproducible, clinically predictive classification of lymphomas. Such an in vivo evaluation of tumor host relationships should provide valuable insights in lymphoma immunobiology.